The human immunodeficiency virus (HIV-1) entry into cells requires tile viral envelope proteins (gp-120/gp4l) and cellular receptors, CD4 and chemokine receptors. Yet puzzles remain. Some strains of HIV can infect cells lacking CD4 on their surface. Despite the recent solving of the crystal structure of a truncated gp- 120 complexed to two-domain CD4 and an Fab fragment (I7b), it is not clear how the complex interacts with the cellular chemokine receptor, nor if this interaction is direct. We've identified an HIV-I antisense gene, that in addition to producing antisense transcripts, could potentially encode a set of chemokine-like proteins. Introduction of this gene into several cell lines that stably express envelope proteins chemokine receptors (CXCR 4) induces cell death and syncytium formation. This indicates that the HIV-1 antisense gene plays a role in events leading to cell fusion and single-cell lysis, perhaps by providing the chemokine motif that participates in interaction with cellular chemokine receptors. We postulate that this virally encoded antisense gene coding for HIV chemokine-like proteins contributes to viral invasion by mediating binding to the cellular chemokine receptor, perhaps in conjunction with gp-120. We plan to investigate this using a bioassay investigating single- cell lysis. In addition, we will further characterize and isolate the HIV chemokine-like protein(s), and investigate the HW-I gene elements contributing to the antisense promoter activity.